PB2650: ALLOANTIBODIES IN VON WILLEBRAND DISEASE: ABOUT 6 CASES IN SOUTHERN TUNISIA
Authors: Amal Chalbaoui, Rahma Mallek, Fatma Megdiche, Faten Kallel, Imen Krichen, Sondes Hdiji, Olfa Kassar, Imen Frikha, Maha Charfi, Imen Ben Amor, Yosra Fakhfekh, Latifa Khelifa, Medhaffar Moez, Choumous Kallel, Moez Elloumi
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: Von Willebrand disease (VWD) is defined as a defective or dysfunctional Von Willebrand Factor (VWF) that mediates platelet adhesion and aggregation at vascular damage sites. A minority of patients, particularly with type 3 VWD, develops alloantibodies to exogenous VWF whose arising complications are challenging. These antibodies make replacement VWF therapy ineffective and even dangerous by producing anaphylactic reactions. Aims: Our study aims to evaluate the clinico-biological, therapeutic and evolutionary characteristics of VWD patients with alloantibodies. Methods: Our study is retrospective, it concerned patients with VWD who developed alloantibodies. Data were recorded from VWD registry which includes patients with VWD in south of Tunisia during 23 years (from January 2000 to December 2022). Anti-VWF and anti-FVIII testing were performed in case of ineffective substitution or when an allergic reaction was occurred during substitution. The screening and the titration of inhibitors were performed by the modified Bethesda method using the coagulation analyzer Sysmex® CS-2100i in the anti-VWF testing and the STA-R® Stago automate in the anti-FVIII testing. Results: During the study period, we collected 89 cases of VWD, 44 cases had type 3. Six patients had alloimmunization: 1 had anti-VWF, 2 had non neutralisant antibodies and 3 had both anti-VWF and anti-FVIII. Thus, anti-VWF was found in 14% of patients with type 3 VWD. Median age at diagnosis of alloimmunization was 30 years [4 years - 47 years] with a female predominance (sex ratio M/F= 0.2). Circumstance of the discovery of alloimmunization were persistent hemorrhagic symptoms despite adequate substitution in 4 cases, a preoperative evaluation in 1 case and an anaphylactic reaction secondary to VWF concentrate administration in 1 case. Our patients were on replacement therapy with cryoprecipitate or VWF/FVIII plasma concentrates (Immunate®). The first patient had a hemarthrosis of the elbow resistant to substitution. Anti-VWF antibodies tested positive with a titre of 5.8 Bethesda units (BU). Recovery test of infused VWF/VLFIII plasma concentrates was carried out with a total absence of recovery for VWF. She was treated with by-passing agent combined with immunosuppressor, which allowed an inhibitor level decrease to 0 UB and a reintroduction of immunate without incident. The 2nd and 3rd patients had a non-neutralizing anti-VWF discovered during an episode of gingivorrhagia resistant to substitution for one of them and during a preoperative evaluation for the other. The anti-VWF and anti-FVIII antibodies’ screening were negative. However, an anti-VWF, considered non-neutralizing, was determined since there were a total absence of recovery for VWF. They were treated with by-passing agent (Novoseven®) combined with corticosteroid therapy with good resolution of the bleeding episode. The last 3 patients had both anti-VWF and anti-FVIII antibodies. They were revealed during an allergic reaction to the replacement therapy in 1 case and a severe bleeding syndrome resistant to substitution in 2 cases. They were treated with by-passing agent combined with immunosuppressor with good clinical resolution. Summary/Conclusion: Alloimunization in VWD is more frequently reported in our patients (14% versus 5-10% in published series). Several types of antibodies were documented. In our knowledge, the coexistence of anti-VWF and anti-FVIII is extremely rare and isn’t yet reported. In this challenging situations, by-passing agents such as Novoseven®, recombinant FVIII and immunosupressive therapy may be useful. Keywords: Bleeding disorder, von Willebrand factor (vWF), Antibody, von Willebrand’s disease